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Open Access Research article

Inhibitor of neuronal nitric oxide synthase improves gas exchange in ventilator-induced lung injury after pneumonectomy

Evgeny V Suborov1, Alexey A Smetkin14, Timofey V Kondratiev1, Andrey Y Valkov23, Vsevolod V Kuzkov14, Mikhail Y Kirov14 and Lars J Bjertnaes1*

Author Affiliations

1 Anesthesia and Critical Care Research Group, Institute of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway

2 Department of Clinical Pathology, University Hospital of Northern Norway, 9038, Tromsø, Norway

3 Institute of Medical Biology, University of Tromsø, 9037, Tromsø, Norway

4 Department of Anesthesiology, Northern State Medical University, Arkhangelsk, Russian Federation

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BMC Anesthesiology 2012, 12:10  doi:10.1186/1471-2253-12-10

Published: 21 June 2012

Abstract

Background

Mechanical ventilation with high tidal volumes may cause ventilator-induced lung injury (VILI) and enhanced generation of nitric oxide (NO). We demonstrated in sheep that pneumonectomy followed by injurious ventilation promotes pulmonary edema. We wished both to test the hypothesis that neuronal NOS (nNOS), which is distributed in airway epithelial and neuronal tissues, could be involved in the pathogenesis of VILI and we also aimed at investigating the influence of an inhibitor of nNOS on the course of VILI after pneumonectomy.

Methods

Anesthetized sheep underwent right pneumonectomy, mechanical ventilation with tidal volumes (VT) of 6 mL/kg and FiO2 0.5, and were subsequently randomized to a protectively ventilated group (PROTV; n = 8) keeping VT and FiO2 unchanged, respiratory rate (RR) 25 inflations/min and PEEP 4 cm H2O for the following 8 hrs; an injuriously ventilated group with VT of 12 mL/kg, zero end-expiratory pressure, and FiO2 and RR unchanged (INJV; n = 8) and a group, which additionally received the inhibitor of nNOS, 7-nitroindazole (NI) 1.0 mg/kg/h intravenously from 2 hours after the commencement of injurious ventilation (INJV + NI; n = 8). We assessed respiratory, hemodynamic and volumetric variables, including both the extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI). We measured plasma nitrite/nitrate (NOx) levels and examined lung biopsies for lung injury score (LIS).

Results

Both the injuriously ventilated groups demonstrated a 2–3-fold rise in EVLWI and PVPI, with no significant effects of NI. In the INJV group, gas exchange deteriorated in parallel with emerging respiratory acidosis, but administration of NI antagonized the derangement of oxygenation and the respiratory acidosis significantly. NOx displayed no significant changes and NI exerted no significant effect on LIS in the INJV group.

Conclusion

Inhibition of nNOS improved gas exchange, but did not reduce lung water extravasation following injurious ventilation after pneumonectomy in sheep.

Keywords:
Pneumonectomy; Mechanical ventilation; nNOS; Pulmonary edema; Sheep; Nitric oxide; Ventilator-induced lung injury; 7-nitroindazole